What are the effects of using apixaban (Eliquis) and clopidogrel (Plavix) together?

From the FDA Drug Label

1. 3 Anticoagulants and Antiplatelet Agents Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk, post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo. The rate of ISTH major bleeding was 2.8% per year with apixaban versus 0. 6% per year with placebo in patients receiving single antiplatelet therapy and was 5.9% per year with apixaban versus 2.5% per year with placebo in those receiving dual antiplatelet therapy. The use of apixaban and clopidogrel together increases the risk of bleeding. In the APPRAISE-2 trial, the rate of major bleeding was higher with apixaban compared to placebo in patients receiving dual antiplatelet therapy, which includes clopidogrel. Key points include:

• Increased risk of bleeding with concomitant use of apixaban and antiplatelet agents, including clopidogrel
• Higher rate of major bleeding with apixaban compared to placebo in patients receiving dual antiplatelet therapy 1

From the Research

Effects of Apixaban and Clopidogrel Combination

The combination of apixaban (Eliquis) and clopidogrel (Plavix) has been studied in various clinical settings, including acute coronary syndromes and atrial fibrillation. The effects of this combination can be summarized as follows:

• Increased risk of bleeding: Studies have consistently shown that the combination of apixaban and clopidogrel increases the risk of major bleeding compared to apixaban alone or clopidogrel alone 2, 3, 4.
• No significant difference in efficacy: The APPRAISE-2 trial found no differential effect of apixaban versus placebo on the composite endpoint of cardiovascular death, myocardial infarction, and ischemic stroke in patients taking aspirin or aspirin plus clopidogrel 2.
• Similar risk of major bleeding compared to rivaroxaban and clopidogrel: A retrospective cohort study found that the concomitant use of apixaban and clopidogrel conferred a similar risk of major bleeding compared to rivaroxaban and clopidogrel 4.

Clinical Considerations

When considering the use of apixaban and clopidogrel together, the following clinical considerations should be taken into account:

• Patient population: The combination of apixaban and clopidogrel may be more suitable for patients with atrial fibrillation undergoing coronary artery stenting, as it has been shown to be effective in reducing the risk of ischemic events in this population 5.
• Dosing and duration: The optimal dosing and duration of apixaban and clopidogrel combination therapy have not been established, and further studies are needed to determine the best approach 5, 3.
• Bleeding risk: The increased risk of bleeding associated with the combination of apixaban and clopidogrel should be carefully considered, and patients should be closely monitored for signs of bleeding 2, 3, 4.

Key Findings

Key findings from the studies include:

• The APPRAISE-2 trial found that apixaban increased Thrombolysis In Myocardial Infarction major bleeding in patients taking aspirin or aspirin plus clopidogrel 2.
• The APPRAISE trial found that apixaban resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding, and a trend toward a reduction in ischemic events compared to placebo 3.
• A retrospective cohort study found that the concomitant use of apixaban and clopidogrel conferred a similar risk of major bleeding compared to rivaroxaban and clopidogrel 4.